Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10/7/1984-24/7/1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: U.S. Department of Transportation Method of Testing Corrosion to Skin
Version / remarks:
October 1, 1979
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
A mixture of sodium dichromate samples, obtained from six different sources was assessed for its potential to cause skin corrosion in accordance with the Department of Transportation´s method. A weight of 0.5 g of crystalline solid test material was applied to the rabbit skin for four hours. An untreated gauze patch was applied to a second skin site, serving as a negative control. In addition, 0.5 g of test material was moistened with 0.5 ml of physiological saline and applied to a third skin site to investigate the effects of wetting the mixture of chrome samples on the skin.
The study guideline is designed to investigate corrosive effects; the design is similar to OECD 404, however the study was terminated at Day 5 when no signs of corrosion were observed. The results of the study are sufficient to classify the substance for skin irritation according to EU criteria.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium dichromate
EC Number:
234-190-3
EC Name:
Sodium dichromate
Cas Number:
10588-01-9
Molecular formula:
Cr2Na2O7
IUPAC Name:
disodium [(oxidodioxochromio)oxy]chromiumoylolate dihydrate
Test material form:
solid: crystalline
Details on test material:
The test material is described as a crystalline solid and was used as a mixture of material obtained from six different sources. The six samples and the respective soures were the following:
Sodium dichromate dihydrate TSS/572/A- British Chrome and Chemicals LTD
Sodium bichromate crystals- Diamond Shamrock Corporation,
Sodium bichromate- Allied Corporation,
Sodium bichromate crystals- Luiqui Stoppani,
Sodium dichromate crystals (dihydrate)- Bayer
Sodium dichromate- Alfa Products
60 g of each sample were mixed to obtain the test substance.

Sample number: 8245-95
Stability: assumed stable for duration of the study
Shelf life: assumed stable for duration of the study
Storage conditions: room temperature in tightly sealed container away from combustible materials

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
males
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm, Belvidere, NJ, USA
- Age at study initiation: 10-12 weeks
- Housing: Individual in suspended stainless steel wire mesh cages
- Diet: Purina laboratory rabbit chow 5326 HF, ad libitum (except while dosing and observation)
- Water: tap water, ad libitum (except while dosing and observation), analysis was performed regularly for Animal Resources Section (SOP ANA-030)
- Acclimation period: At least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 4 °C
- Humidity: 50 ± 15 %
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 10/7/84 To: 24/7/84

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g without physiological saline; 0.5 g moistened with 0.5 ml physiological saline
- Concentration of solution: 1 g/ml (in vehicle)

VEHICLE
- Amount(s) applied: 0.5 ml saline
- Lot/batch no.: sample No. 8245-79E
Duration of treatment / exposure:
4 hours
Observation period:
5 days
Number of animals:
Six
Details on study design:
TEST SITE
- Area of exposure: 1 square inch
- Type of wrap if used: the test substance was held in place with a 12 ply surgical gauze patch and secured with 1 inch wide strips of Blenderm (3M Company, Medical Products Division, St. Paul, MN) surgical tape at the four edges, leaving the center of the gauze patch nonoccluded.
The negative control site was covered with an untreated 12 ply surgical gauze patch.
The entire trunk of the animal was covered with an impervious material (such as Saran Wrap) for a 4 hour period of exposure. The Saran Wrap was secured by wrapping several long strips of athletic adhesive tape around the trunk of the animal. The impervious material aids in maintaining the position of the patches and retards evaporation of volatile test substances.
A Saf-T-Shiled collar was fitted and fastended around the neck of each test animal. The collar remained in place for the 4 hour exposure period. The collars were utilized to prevent removal of wrappings and patches by the animals, while allowing the animals food and water ad libitum.

OBSERVATIONS:
Immediately after the patches were removed and the sites were marked, observations of the test and control sites were made. Observations were again made at the end of a total of 48 hours (44 hours after the first reading).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): If required
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
- 4 and 48 hours after dosing
- a conclusive assessment of the extent of damage to the skin could not be made after 48 hours, therefore, daily observations of the skin sites were made to day 5 after exposure.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Score:
4
Reversibility:
not fully reversible within: 5 days
Remarks on result:
other: necrosis (superficial focal point in center of reddened area)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 96 hours
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 96 hours
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 96 hours
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 96 hours
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 96 hours
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 96 hours
Score:
2
Reversibility:
not fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #5
Time point:
48 h
Score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 96 hours
Score:
1
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 96 hours
Score:
1
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 96 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 96 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 96 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 96 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Please refer to the field any other information on results incl. tables

Any other information on results incl. tables

No dermal reactions were seen in animals treated with the control patches.

With the dry test material, signs of irritation were limited to moderate erythema (Grade 2) in two animals which declied in severity, but were still present at the end of the study period (Grade 1). Very weak orange staining of the skin site was observed in all six animals 4 hours after exposure.

Strong orange staining of the application site was seen in animals exposed to the moistened test material 4 hours after exposure. Signs of irritation were seen from 48 hours in animals exposed to the moistened test material. Grade 2 erythema was seen in all animals from 48 hours and persisted to study termination; Grade 4 erythema was seen in one animal at 48 hours only. Grade 1 -3 oedema was observed in five animals; findings declined in severity and were not apparent at study termination at 120 hours. Focal necrosis was additionally apparent in one animal at 48 hours but not at later time points, demonstrating rapid reversibility.

Mean scores for skin irritation

Application

Observation

4h

48h

72h

96h

120h

Dry

Erythema

0.00

0.67

0.67

0.50

0.30

Oedema

0.00

0.00

0.00

0.00

0.00

Moistened

Erythema

0.00

2.33*

2.00

2.00

2.00

Oedema

0.00

1.50

0.67

0.33

0.00

Control

Erythema

0.00

0.00

0.00

0.00

0.00

Oedema

0.00

0.00

0.00

0.00

0.00

* necrosis (superficial focal point in center of reddened area)

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Sodium dichromate induced mild to strong orange staining of the application site and local irritation (Grade 2) were seen following application of the moistened test material. This irritation was not reversible within the 5 day study period. There was no evidence of corrosivity.
Since the moderate local irritation (Grade 2) was not reversible within 5 days and no further observation time points were included, it remains unclear whether the local irritation would be reversible or persistent. Based on this, a worst case classification is proposed. According to the classification criteria of CLP regulation (EC) 1272/2008 and subsequent regulations sodium dichromate is classified as Category 2 Irritant with the signal word Warning and the hazard statement H315: Causes skin irritation.
Executive summary:

The dermal irritancy of sodium dichromate was investigated in the rabbit; the test material was administered dry or moistened with saline.

No dermal reactions were seen in animals treated with the control patches.

Relatively mild local dermal reactions and mild orange staining were seen following application of the dry test material. Strong orange staining of the application site and local irritation (erythema and oedema) were seen following application of the moistened test material; irritation was declining in severity but was not reversible within the 120-hour study period. There was no evidence of corrosivity, however the test material was shown to be a skin irritant.

Although the study design (in respect of observation time points and observation period) is not completely in line with the recommendations of OECD 404, this study is considered to be valid.

Since the moderate local irritation was not reversible within 5 days and no further observation time points were included, it remains unclear whether the local irritation would be reversible or persistent. Based on this, a worst case classification is proposed. According to the classification criteria of CLP regulation (EC) 1272/2008 and subsequent regulations sodium dichromate is classified as Category 2 Irritant with the signal word Warning and the hazard statement H315: Causes skin irritation.